基于复方配伍环境探究番红花去柱头花部治疗高尿酸血症合并痛风性关节炎的药效与作用机制  

Exploring Efficacy and Mechanism of Saffron Floral Bio-residues for Treatment of Hyperuricemia Combined with Gouty Arthritis Based on Compound Compatibility Environment

作　　者：武济萍 李晴晴 王岚[1] 殷小杰[1] 冯淑仪[3] 王志昊 梁日欣[1] 杨滨[1] 李志勇 WU Jiping;LI Qingqing;WANG Lan;YIN Xiaojie;FENG Shuyi;WANG Zhihao;LIANG Rixin;YANG Bin;LI Zhiyong(State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs,Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Shandong University of Traditional Chinese Medicine(TCM),Jinan 250355,China;Experimental Research Center,China Academy of Chinese Medical Sciences,Beijing 100700,China;Prescription and Drug Compatibility and Function Research Laboratory Supported by Shanxi Provincial Administration of TCM,Shanxi University of Chinese Medicine,Jinzhong 030619,China)

机构地区：[1]中国中医科学院中药研究所,道地药材品质保障与资源持续利用全国重点实验室,北京100700 [2]山东中医药大学,济南250355 [3]中国中医科学院医学实验中心,北京100700 [4]山西中医药大学,方药配伍及功用山西省中医药管理局重点研究室,山西晋中030619

出　　处：《中国实验方剂学杂志》2024年第23期129-140,共12页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：中国中医科学院科技创新工程项目(CI2023E002,CI2023E001TS);国家重点研发计划项目(2018YFC1706103)。

摘　　要：目的:在复方配伍环境下,探究番红花去柱头花部(SFB)治疗高尿酸血症(HUA)合并痛风性关节炎(GA)的药效与作用机制。方法:基于数据分析和网络靶点距离计算,筛选复方及SFB的对照中药。80只SD大鼠适应性喂养7 d后,随机取10只大鼠作为空白组,其余70只大鼠腹腔注射3%氧嗪酸钾并灌胃1%腺嘌呤,连续14 d,第13天于大鼠右踝关节腔注射2.5%尿酸钠溶液,诱导HUA合并GA模型。将成模大鼠随机分为模型组、苯溴马隆组(0.02 g·kg^(-1))、痛风舒片组(9 g·kg^(-1))、痛风舒颗粒组(9 g·kg^(-1))、SFB颗粒组(3.6 g·kg^(-1))、车前子颗粒组(3.6 g·kg^(-1))和新方组(SFB替代痛风舒颗粒中的车前子,9 g·kg^(-1)),每组10只。各给药组按剂量灌胃相应药物,空白组和模型组灌胃等体积蒸馏水,1次/d,连续14 d,造模期间同步给药。给药结束后,检查大鼠步态、踝关节肿胀度和机械痛阈值变化,并检测血清尿酸、肌酐、尿素氮、黄嘌呤氧化酶(XOD);酶联免疫吸附测定法(ELSIA)检测大鼠血清肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β和IL-6水平;苏木素-伊红(HE)染色观察大鼠肝、肾和踝关节病理变化;蛋白免疫印迹法(Western blot)检测大鼠肾脏尿酸转运体1(URAT1)、葡萄糖转运体9(GLUT9)、有机阴离子转运体1(OAT1)、三磷酸腺苷(ATP)结合盒转运蛋白G2(ABCG2)及肝脏XOD蛋白的表达水平。结果:通过网络药理学分析,确定车前子作为候选对照药,痛风舒片作为复方配伍环境,用于探究SFB的降血酸和治疗GA疗效。动物实验表明,与空白组比较,模型组的步态评分和关节肿胀度均显著升高,机械痛阈显著降低(P<0.01);与模型组比较,各给药组大鼠步态评分、关节肿胀度及机械痛阈均有不同程度改善。生化指标检测结果显示,与空白组比较,模型组大鼠的血清尿酸、肌酐、尿素氮、XOD水平均显著上升(P<0.01);与模型组比较,各给药组大鼠血清尿酸、XOD水平�Objective:To investigate the efficacy and mechanism of saffron floral bio-residues(SFB)in the treatment of hyperuricemia(HUA)combined with gouty arthritis(GA)in a compound compatibility setting.Method:Screening candidate control Chinese medicines for compound and SFB based on network target distance calculation and data analysis.After adaptive feeding of 80 SD rats for 7 days,10 rats were randomly selected as the blank group,while the remaining 70 rats were intraperitoneally injected with 3%potassium oxonate and orally administered with 1%adenine for 14 consecutive days.On the 13th day,rats were injected with 2.5%sodium urate solution into the right ankle joint cavity to induce swelling of the joint capsule on the opposite side,inducing a HUA combined with GA model.At the same time,the modeling rats were randomly divided into 7 groups,including the model group,benzbromarone group(positive drug,0.02 g·kg^(-1)),Tongfengshu tablets group(9 g·kg^(-1)),Tongfengshu granules group(9 g·kg^(-1)),SFB granules group(3.6 g·kg^(-1)),Plantaginis Semen granules group(3.6 g·kg^(-1)),and new formula group(SFB replacing Plantaginis Semen in Tongfengshu granules,9 g·kg^(-1)),with 10 rats in each group.Each treatment group was orally administered with the corresponding drugs according to body weight,while the control and model groups were given equal volume of distilled water by gavage once a day for 14 consecutive days.After 14 days of synchronous administration and modeling,changes in gait,ankle joint swelling and mechanical pain threshold in rats were observed,and serum uric acid,creatinine,urea nitrogen and xanthine oxidase(XOD)were measured.Enzyme-linked immunosorbent assay(ELSIA)was used to detect the levels of tumor necrosis factor(TNF)-α,interleukin(IL)-1βand IL-6 in rat serum,hematoxylin-eosin(HE)staining was used to observe the pathological changes in the liver,kidney and ankle joints of rats,Western blot was used to detect the expression levels of uric acid transporter 1(URAT1),glucose transporter 9(GLUT9),organic

关 键 词：中药新资源 番红花去柱头花部 高尿酸血症 痛风性关节炎 复方配伍 网络药理学 

分 类 号：R22[医药卫生—中医基础理论] R28[医药卫生—中医学] R931R971.1